Materials Today Bio
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2024
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IF 8.7
Changxing Liu,Yawei Sun,Dengju Li,Fan Wang,Haojue Wang,Senbo An,Shui Sun
Osteoarthritis (OA) is characterized by progressive and irreversible damage to the articular cartilage and a consecutive inflammatory response. However, the majority of clinical drugs for OA treatment only alleviate symptoms without addressing the fundamental pathology. To mitigate this issue, we developed an inflammation-responsive carrier and encapsulated bioactive material, namely, LDH@TAGel. The LDH@TAGel was designed with anti-inflammatory and antioxidative abilities, aiming to directly address the pathology of cartilage damage. In particular, LDH was confirmed to restore the ECM secretion function of damaged chondrocytes and attenuate the expression of catabolic matrix metalloproteinases (Mmps). While TAGel showed antioxidant properties by scavenging ROS directly. In vitro evaluation revealed that the LDH@TAGel could protect chondrocytes from inflammation-induced oxidative stress and apoptosis via the Nrf2/Keap1 system and Pi3k-Akt pathway. In vivo experiments demonstrated that the LDH@TAGel could alleviated the degeneration and degradation of cartilage induced by anterior cruciate ligament transection (ACLT). The OARSI scores indicating OA severity decreased significantly after three weeks of intervention. Moreover, the IVIS image revealed that LDH@TAGel enhances the controlled release of LDH in a manner that can be customized according to the severity of OA, allowing adaptive, precise treatment. In summary, this novel design effectively alleviates the underlying pathological causes of OA-related cartilage damage and has emerged as a promising biomaterial for adaptive, cause-targeted OA therapies.
研究领域:
生物材料
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组织工程
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骨科
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-15
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IF 10.6
Cao Haifei,Li Wanxin,Zhang Hao,Hong Lihui,Feng Xiaoxiao,Gao Xuzhu,Li Hongye,Lv Nanning,Liu Mingming
Background and aims Osteoarthritis (OA) is a prevalent degenerative joint disorder, marked by the progressive degeneration of joint cartilage, synovial inflammation, and subchondral bone hyperplasia. The synovial tissue plays a pivotal role in cartilage regulation. Exosomes (EXOs), small membrane-bound vesicles released by cells into the extracellular space, are crucial in mediating intercellular communication and facilitating the exchange of information between tissues. Our study aimed to devise a hydrogel microsphere infused with SOD3-enriched exosomes (S-EXOs) to protect cartilage and introduce a novel, effective approach for OA treatment. Materials and methods We analyzed single-cell sequencing data from 4247 cells obtained from the GEO database. Techniques such as PCR, Western Blot, immunofluorescence (IF), and assays to measure oxidative stress levels were employed to validate the cartilage-protective properties of the identified key protein, SOD3. In vivo, OA mice received intra-articular injections of S-EXOs bearing hydrogel microspheres, and the effectiveness was assessed using safranine O (S.O) staining and IF. Results Single-cell sequencing data analysis suggested that the synovium influences cartilage via the exocrine release of SOD3. Our findings revealed that purified S-EXOs enhanced antioxidant capacity of chondrocytes, and maintained extracellular matrix metabolism stability. The S-EXO group showed a significant reduction in mitoROS and ROS levels by 164.2% ( P < 0.0001) and 142.7% ( P < 0.0001), respectively, compared to the IL-1β group. Furthermore, the S-EXO group exhibited increased COL II and ACAN levels, with increments of 2.1-fold ( P < 0.0001) and 3.1-fold ( P < 0.0001), respectively, over the IL-1β group. Additionally, the S-EXO group showed a decrease in MMP13 and ADAMTS5 protein expression by 42.3% ( P < 0.0001) and 44.4% ( P < 0.0001), respectively. It was found that S-EXO-containing hydrogel microspheres could effectively deliver SOD3 to cartilage and significantly mitigate OA progression. The OARSI score in the S-EXO microsphere group markedly decreased ( P < 0.0001) compared to the OA group. Conclusion The study demonstrated that the S-EXOs secreted by synovial fibroblasts exert a protective effect on chondrocytes, and microspheres laden with S-EXOs offer a promising therapeutic alternative for OA treatment.
研究领域:
骨科
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分子生物学
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Shibo Xu,Linna Chang,Xingjun Zhao,Yanan Hu,Yiyi Lin,Zhenhua Chen,Xiuli Ren,Xifan Mei
Osteoarthritis (OA), a widespread degenerative disease characterized by cartilage destruction, has emerged as a public health challenge in the current aging society. In addition to applied steroids and surgery, near-infrared (NIR) sensitive nano-enzyme for the treatment of osteoarthritis through mitochondrial repair and cartilage protection is attractive and promising. In this study, a NIR sensitive multifunctional heterostructure (EGCG (Epigallocatechin gallate) decorated Au-Ag nano-jars ( [email protected] )) was introduced as an enzyme-sensitive active nanoplatform for the treatment of osteoarthritis. Molecular biology results indicated that [email protected] possesses intrinsic properties of anti-oxidative stress and was able to reduce the apoptosis rate of chondrocytes by 83.3%. The area of the intra-articular joint cavity injected with [email protected] can be elevated to 46.6 °C under NIR to promote the release of EGCG further to induce cartilage regeneration. X-ray radiography and section staining showed that [email protected] reduced cartilage damage and decreased OARSI scores by approximately 52% after 8 weeks of treatment in a surgically induced OA model. The results demonstrated that this multifunctional enzyme-like nanoplatform with a synergistic NIR sensitive property to facilitate cartilage migration and regeneration repair provides a promising OA treatment strategy. Statement of significance 1. NIR-sensitive nano-enzyme is gaining much attention in the field of biomedical materials . 2. EGCG decorated Au-Ag nano-heterostructures were utilized as NIR-sensitive nano-enzymes for the treatment of osteoarthritis through mitochondrial repair and cartilage protection. 3. The obtained multifunctional Au-Ag nano-heterostructures are promising for osteoarthritis treatment.
研究领域:
生物医学材料
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纳米技术
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骨科
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分子生物学
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Shibo Xu,Yiyi Lin,Xingjun Zhao,Zepeng Liang,Yanan Hu,Zhenhua Chen,Xiuli Ren,Xifan Mei
Osteoarthritis (OA) is one of the leading causes of chronic disability in the elderly. Effective clinical interventions for OA are still lacking, and new therapeutic measures are urgently needed. The emerging near-infrared light (NIR) sensitive nanozymes are attractive for their great potential and appeal in treating OA by repairing mitochondrial function and improving impaired autophagic flux. In this study, a NIR-sensitive tea polyphenol-modified zirconium-based porphyrin metal–organic framework ( [email protected] ) was introduced as a multifunctional nanoplatform for the treatment of OA. TEM and EDS mapping revealed that gold nanoclusters were uniformly distributed on the surface of the spherical particles. Electron spin resonance (ESR) analysis revealed that nanozymes could alleviate different types of oxidative stress. Molecular biology indicated that [email protected] reduced chondrocyte apoptosis and increased chondrocyte metabolism by 80.7%. An increase in chondrocyte-expressed type II collagen and proteoglycan content ensues. Injection of [email protected] effectively raised the joint temperature to 46.9 °C and controlled drug delivery under NIR excitation. Section staining revealed that eight weeks of intervention decreased the OARSI score in OA rats by approximately 67.0%. Transmission electron microscopy confirmed a significant improvement in intracellular mitochondrial morphology. The present study provides evidence that modifiable multifunctional nanozymes effectively repair cartilage-damaged mitochondria and promote cartilage regeneration, representing an appealing therapeutic strategy for OA.
研究领域:
纳米技术
·
生物医学工程
·
材料科学
·
骨科
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）